Department of Chemical Engineering, South Tehran Branch, Islamic Azad University, Tehran, Iran.
Computational Nanobiotechnology Laboratory, Department of Life Sciences Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran.
J Cell Biochem. 2018 Nov;119(11):9205-9216. doi: 10.1002/jcb.27187. Epub 2018 Aug 4.
The cationic antimicrobial peptide GF-17, a 17-mer-derived peptide from human cathelicidin LL-37, has a significant strength in the killing of the methicillin-resistant Staphylococcus aureus and Escherichia coli strains. Herein, we conducted a series of all-atom molecular dynamics simulations to investigate the ability of GF-17 in perturbing the model membranes of the gram-positive, S. aureus, and gram-negative, E. coli, bacteria. We also explored the contributions of the specific residues in the peptide activity. The molecular dynamics results indicated that the peptide is stabilized on the membrane surface and rapidly binds to the phosphate headgroups of the model membranes through the electrostatic interactions and hydrogen bonds. Furthermore, both polar and nonpolar interactions are energetically favored for the binding with the membrane surface. The research also revealed the important roles of the phenylalanine residues in the early insertion of the peptide into the bacterial model membranes. In addition, the results demonstrated that the central residues Arg23 and Lys25 played a critical role in the binding of GF-17 to both gram-negative and gram-positive model membranes, in excellent agreement with experimental studies. This study emphasizes on the pivotal role of basic residues in prompt association of the peptide on the model membrane surface and on the significance of residues Phe17, Ile24, Phe27, and Val32 in hydrophobic interactions. Therefore, our observations provide insights into the membrane-GF-17 interactions at atomic details that are useful to develop potent antimicrobial peptides targeting multidrug-resistant bacteria.
阳离子抗菌肽 GF-17 是一种源自人源抗菌肽 LL-37 的 17 肽，对耐甲氧西林金黄色葡萄球菌和大肠杆菌菌株具有很强的杀伤能力。在此，我们进行了一系列全原子分子动力学模拟，以研究 GF-17 干扰革兰阳性菌金黄色葡萄球菌和革兰阴性菌大肠杆菌模型膜的能力。我们还探讨了肽活性中特定残基的贡献。分子动力学结果表明，该肽在膜表面稳定，并通过静电相互作用和氢键迅速与模型膜的磷酸头部结合。此外，极性和非极性相互作用都有利于与膜表面的结合。研究还揭示了苯丙氨酸残基在肽早期插入细菌模型膜中的重要作用。此外，结果表明，中央残基 Arg23 和 Lys25 在 GF-17 与革兰阴性和革兰阳性模型膜的结合中起着关键作用，这与实验研究结果非常吻合。这项研究强调了碱性残基在肽迅速与模型膜表面结合中的关键作用，以及残基 Phe17、Ile24、Phe27 和 Val32 在疏水性相互作用中的重要性。因此，我们的观察结果提供了关于膜-GF-17 相互作用的原子细节的见解，这对于开发针对多药耐药菌的有效抗菌肽具有重要意义。
